Laser energy, employed as a focused or transmitted via optical fibers, has been demonstrated in vitro, in vivo in animal models, and more recently in vivo in human patients to be capable of ablating atherosclerotic lesions responsible for stenosis or total occlusion of peripheral and coronary arteries. Although the interaction between laser light and the atherosclerotic lesion has been investigated in some detail, the effect of laser light on vascular smooth muscle has not been previously studied. Accordingly, the aims of this proposal are as follows: 1) to determine the effect of continuous wave (CW) laser- irradiation on vascular smooth muscle; 2) to determine the effect of pulsed laser irradiation on vascular smooth muscle; 3) to investigate the extent to which either the effects of CW or pulsed laser irradiation on vascular smooth muscle are wavelength-dependent; 4) to determine the relationship between laser-induced vasomotor reactivity and thermal behavior of the irradiated segment of vascular smooth muscle; 5) to establish the relationship between the vector and magnitude of laser-induced vasomotor reactivity and the functional and anatomic status of the endothelial layer of the irradiated segment of vascular smooth muscle; and 6) to determine the extent to which laser-induced vasomotion can be modified by various pharmacologic agonists and antagonists. To accomplish these specific aims, a series of in vitro and in vivo experiments will be performed using CW (argon, Nd:YAG) and pulsed (excimer, tuneable dye) lasers. For in vitro experiments, laser irradiation will be delivered to isolated ring segments of aorta obtained from healthy and atherosclerotic New Zealand white rabbits and mounted isometrically in Krebs bicarbonate buffer. For in vivo experiments, laser irradiation will be delivered percutaneously via optical fibers in normal New Zealand white rabbits and rabbits and microswine with atherosclerotic lesions induced by an atherogenic diet and balloon-endothelial denudation. From a fundamental standpoint, the experiments described in this proposal will establish the range of vascular smooth muscle responses to laser irradiation and provide insight regarding the responsible mechanisms. From a practical standpoint, these experiments may have important implications regarding the choice of lasers and the manner in which such lasers are employed for clinical purposes.